Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

53 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vaccine-Elicited CD4 T Cells Induce Immunopathology Following Chronic LCMV Infection

ABSTRACT: CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. Here we evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality following challenge with a persistent form of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. Splenic GP66-specific CD4 T cells from mice immunized with either a LMwt vaccine (sham) or LMgp61 vaccine (CD4 vaccine) were purified by FACS on day 8 post-infection with LCMV clone 13

ORGANISM(S): Mus musculus

SUBMITTER: Nicholas Provine

PROVIDER: E-GEOD-63825 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression data from virus-specific mouse Th1 and Tfh CD4 T cell subsets after LCMV infection

Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here. The SMARTA TCR transgenic / adptive transfer system was used to identify and sort subsets of antigen-specific CD4 T cells (based on their expression of Ly6c and CXCR5) elicited after acute infection with LCMV (Arm).

2013-04-22 | E-GEOD-43863 | biostudies-arrayexpress

Transcription profiling of mouse vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

Project description:Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection. A paper including data analysis of these experiments has been accepted for publication (Robert J. Johnston et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of follicular helper CD4 T cell differentiation). Experiment Overall Design: Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high), versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.

2009-08-07 | E-GEOD-16697 | biostudies-arrayexpress

Whole mouse genome analysis of LCMV-specific CD4 and CD8 T cells throughout acute and chronic LCMV infection.

Project description:CD4 and CD8 T cells display functional defects during chronic infection such as loss of certain cytokines. Recent studies have suggested that CD4 T cells may actually gain other functions, however. Here, we analyzed gene expression profiles from LCMV-specific CD4 and CD8 T cells throughout the response to either acute LCMV or chronic LCMV infection. This alllowed us to identify CD4-specific changes during chronic infection compared to acute infection but also revealed shared core regulators between CD4 and CD8 T cells. LCMV-specific CD4 and CD8 T cells were isolated 6, 8, 15 and 30 days post infection with LCMV Armstrong or LCMV clone 13. Naïve CD4 and CD8 T cells were also isolated from naïve mice as comparisons. Four replicates of each sample were hybridized. The only exception is LCMV-specific CD4 T cells isolated 6 days post infection with LCMV-Arm where only three replicates were hybridized.

2012-12-12 | E-GEOD-30431 | biostudies-arrayexpress

Longitudinal expression data from CD4+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

Project description:During acute viral infections, naïve CD4+ T cells differentiate into effector CD4+ T cells and, after viral control, into memory CD4+ T cells. Memory CD4+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD4+ T cells become less functional. To compare the development of functional memory T cells with poorly functional T cells from chronic viral infection, we generated longitudinal transcriptional profiles for each. Naive CD44Lo CD4+ T cells were isolated and sorted from uninfected C57BL/6 mice and H2-IAb GP66-specific CD4+ T cells were sorted using MHC-II tetramers at d6, 8, 15, and 30 p.i. with either LCMV Arm or LCMV clone 13. RNA from these CD4+ T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays.

2014-10-24 | E-GEOD-41866 | biostudies-arrayexpress

Regulatory and effector T cells in Lymphocytic choriomeningitis virus WE infection

Project description:In this study, we determined the signature of CD4+Foxp3- effector T cells and CD4+Foxp3+ Treg cells in naive animals and following LCMV WE infection. In addition, transcriptional signatures were determined in CXCR3+ CD4+Foxp3+ Treg cells arising in Th1 settings following LCMV infection.

2020-03-11 | E-MTAB-8861 | biostudies-arrayexpress

Vaccine-Elicited CD4 T Cells Induce Immunopathology Following Chronic LCMV Infection

Project description:CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. Here we evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality following challenge with a persistent form of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.

2014-12-04 | GSE63825 | GEO

Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.

2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress

Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh

Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo polyclonal GC Tfh vs Tfh vs Non-Tfh eight days after LCMV viral infection. Analysis of in vivo follicular helper CD4 T cells (CXCR5high GL7low), versus germinal center follicular helper CD4 T cells (CXCR5hi GL7hi), versus non-follicular helper CD4 T cells (CXCR5low) eight days after viral infection.

2010-04-28 | E-GEOD-21380 | biostudies-arrayexpress

RNA-Seq of mouse CD4+ T cells to analyse CD4+ TERM cells

Project description:Transcriptional profiles of naive, memory and TERM (early responder memory T cells) CD4+ T cells from control and LCMV memory mice.

2024-05-27 | E-MTAB-11521 | biostudies-arrayexpress

T cell UTX promotes Tfh-mediated clearance of persistent virus infection

Project description:Epigenetic changes, including histone methylation, control T cell differentiation and memory formation, though the enzymes that mediate these processes are not clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, promotes the generation of T follicular helper (Tfh) cells, a CD4+ T cell subset essential for B cell antibody generation and clearance of chronic viral infections. Mice with T cell specific UTX deletion (UTX TKO mice) had fewer Tfh cells, showed defective germinal center formation, lacked virus-specific IgG production, and were unable to resolve chronic lymphocytic choriomeningitis virus infection. In UTX TKO T cells, decreased expression of IL-6R±, and other Tfh-related loci, was associated with increased H3K27 methylation. Additionally, Turner Syndrome subjects, who are predisposed to chronic ear infections, have reduced UTX expression in immune cells and decreased Tfh frequency. Thus, we identify a critical link between UTX in T cells and immunity to infection. Mice were infected with chronic LCMV and sorted for Tfh on day 21 pi (sorted for: CD4+CXCR5+CD62Llo T cell). ChIP-Seq and RNA-Seq on WT and Utx KO cells.

2015-09-01 | E-GEOD-64969 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data